Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer
Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer
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DOI：
10.1186/s13058-019-1235-8
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发表时间：
2019-12-19
影响因子：
7.4
通讯作者：
Shaw, Jacqueline A.
中科院分区：
文献类型：
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作者：
Fernandez-Garcia, Daniel;Hills, Allison;Shaw, Jacqueline A.
背景资料：乳腺癌（BC）是女性中最常见的癌症，尽管引入了新的筛查方案、疗法和监测技术，仍需要开发更有用的检测方法来监测治疗反应并为临床决策提供信息。本研究的目的是将循环无细胞DNA（cfDNA）和循环肿瘤细胞（CTC）与传统的乳腺癌血液生物标志物进行比较方法：对194例经放射学确诊的女性乳腺癌患者进行回顾性分析，并与2006年1月至2007年12月在我院行乳腺癌根治术的患者进行比较。通过qPCR测定总cfDNA水平，并与CTC计数和CA 15 -3和碱性磷酸酶（AP）值进行比较。将血液生物标志物数据与传统肿瘤标志物、治疗和反应（如通过RECIST和生存评估）进行比较，使用非参数统计假设检验来检查差异，相关性分析和线性回归来确定相关性并描述其效果。Logistic回归和受试者工作特征曲线使用ROC曲线来估计生物标志物和临床结果之间的关系的强度，并针对标准差进行值归一化以使生物标志物值具有可比性。Kaplan-Meier估计和考克斯回归模型用于评估生存率。在适当的情况下进行单变量和多变量模型。多变量分析表明，总cfDNA的量（p值= 0.024，HR = 1.199，CI = 1.024-1.405）和CTC数量（p值= 0.001，HR = 1.243，CI = 1.088-1.421）是总生存期（OS）的预测因子，而总cfDNA水平是无进展生存期（PFS）的唯一预测因子（p值= 0.042，HR = 1.193，CI = 1.007-1.415）和疾病缓解（单变量和多变量分析分别为HR = 15.917，HR = 12.481）。最后，CTC和cfDNA的组合分析比两种常规生物标志物（CA 15 -3和AP）的组合更能提供用于预测OS的信息。结论：总cfDNA水平的测量是比CTC计数更简单且更便宜的生物标志物，其与PFS、OS和MBC中的响应相关，这表明廉价且简单的基于血液的测试的潜在临床应用。
Background: Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making.The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC).Methods: One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH (R) CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival.Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan-Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate.Results: Multivariate analysis showed that both the amount of total cfDNA (p value = 0.024, HR = 1.199, CI = 1.024-1.405) and the number of CTCs (p value = 0.001, HR = 1.243, CI = 1.088-1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value = 0.042, HR = 1.193, CI = 1.007-1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS.Conclusion: Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.